The objectives of this proposal are to develop and evaluate a biotyping system for Candida albicans, to correlate virulence with biotype and to investigate the biotypes associated with colonization and infection of humans. Preliminary data show that natural variation in the assimilation of carbon and nitrogen compounds, surface antigens, and susceptibility to drugs can be utilized to develop a biotyping system. The following three tests may be used to form the basis of a typing system: assimilation of melezitose, susceptibility to 5-fluorocytosine, and serogrouping. Three to five additional tests suitable for inclusion in a typing system will be sought through biochemical and susceptibility studies of strains of C. albicans. Each test will be evaluated for reproducibility and stability of results both through analysis of laboratory strains and analysis of multiple isolates from individual patients. The physiological basis for divergent results and the mutation rate will also be studied. Pathogenicity of the biotypes will be assessed through virulence studies in mice, through analysis of proteolytic enzymes, and by correlation of biotypes with human disease. The epidemiological significance of the system will be evaluated by determining the reliability of the biotyping system, the biotypes colonizing healthy individuals, the biotypes associated with disease, and the ability of the biotyping system to assist in determining whether two strains come from the same or different sources. The clinical significance of the biotyping system will be assessed by correlation of the epidemiological and pathogenicity data. Development and evaluation of the typing system as proposed will lead to a better understanding of the pathogenicity of this microbe and better management of patients at risk of developing an infection with C. albicans.